OVERALL OBJECTIVES: (1) Continue to study the biochemical, physical and biological properties of antitumor glutaminases, with emphasis on those characteristics which may be important for good therapeutic activity. (2) Bacterial enzymes have been isolated in our laboratory which degrade plasma histidine, serine and arginine when injected in mice. We will purify these enzymes and study their effects on growth of experimental tumors. (3) We will test known organisms and those isolated from soil by the enrichment culture technique for production of the following enzymes: (a) a cystine-degrading enzyme capable of depleting plasma cystine in vivo; (b) enzymes which will attack the polyamines (putrescine, spermidine and spermine) in vivo. We wish to test the antineoplastic effects of polyamine-degrading enzymes alone and in combination with chemical analogues, which inhibit polyamine biosynthesis; (c) a neuraminidase with optimal activity at physiological pH and other characteristics which are needed for maximum therapeutic usefulness. (4) Study the effects of prolonged enzyme treatment on plasma and tissue concentrations of their substrates in animals. (5) Evaluate the antineoplastic efficacy of single- and multi-enzyme therapy, as well as enzyme therapy combined with appropriate chemical analogs. (6) Determine the toxicity of new enzymes in animals. (7) If needed, chemically or physically modify the enzymes to extend their biological half-life, reduce their immunogenicity and improve their distribution outside the vascular space so as to increase their effectiveness on solid tumors.